An in vitro alveolar macrophage assay for predicting the short-term inhalation toxicity of nanomaterials

Wiemann, Martin; Vennemann, Antje; Sauer, Ursula G.; Wiench, Karin; Ma-Hock, Lan; Landsiedel, Robert

doi:10.1186/s12951-016-0164-2

Journal of Nanobiotechnology

Table 3 Comparison of significant in vitro LOAECs to NOAECs and LOAECs recorded in rat short-term inhalation studies

From: An in vitro alveolar macrophage assay for predicting the short-term inhalation toxicity of nanomaterials

Test materials			In vitro NR8383 AM assay									STIS
Class	Name	BET [m²/g]	LOAEC [µg/mL]				LOAEC [mm²/mL]					NOAEC [mg/m³]	LOAEC [mg/m³]^a	Ref^d
Class	Name	BET [m²/g]	LDH	GLU	TNF-α	ROS H₂O₂	LDH	GLU	TNF-α	ROS H₂O₂	Threshold <6000	Threshold <10		Ref^d
Micron-sized crystalline silica	Quartz DQ12	8	90	90	45	n.s.	720	720	360	n.s.	3	*0.1*	*1.0*	[106]
Active metal oxide NMs	TiO₂ NM-105	47	90	90	90	n.s.	4230	4230	4230	n.s.	3	<2	*2.0*	[10]
	ZnO NM-111	15	5.6	90	22.5	n.s.	84	1350	338	n.s.	3	*0.5*	*2.5*	[11]
	nano-CeO₂	33	90	180	45	n.s.	2970	n.s.	1485	n.s.	2	*0.5*	*2.5*	[11]
	Al-doped CeO₂	46	45	90	22.5	n.s.	2070	4140	1035	n.s.	3	*0.5*	*2.0*	[11]
	CeO₂ NM-211	66	90	180	22.5	n.s.	5940	n.s.	1485	n.s.	2	*<0.5*	*5.0*	[111]
	CeO₂ NM-212	27	90	180	22.5	n.s.	2430	n.s.	608	n.s.	2	*<0.5*	*5.0*	[111]
Amorphous SiO₂ NMs	SiO₂.naked	200	22.5	45	22.5	45	4500	9000	4500	9000	2	*2.5*	10	[11]
	SiO₂.PEG	200	90	90	90	180	18000	18000	18000	36000	0	≥50	n.r.	[11]
	SiO₂.amino	200	45	45	22.5	180	9000	9000	4500	36000	1	≥50	n.r.	[11]
	SiO₂.phosphate	200	90	180	90	45	18000	n.s.	18000	9000	0	≥50	n.r.	[11]
	SiO₂ NM-200	189	22.5	22.5	22.5	n.s.	4253	4253	4253	n.s.	3	1	5	[80]
	SiO₂ NM-203	200	22.5	22.5	22.5	n.s.	4500	4500	4500	n.s.	3	1	5	[80]
Passive metal oxide and metal sulphate NMs	AlOOH	105	90	n.s.	180	n.s.	9450	n.s.	18900	n.s.	0	(3)^b	(28)^b	[58]
	BaSO₄	41	n.s.	n.s.	n.s.	n.s.	n.s.	n.s.	n.s.	n.s.	0	≥50	n.r.	[11]
	Fe₂O₃ (hematite)	98	n.s.	n.s.	90	n.s.	n.s.	n.s.	8266	n.s.	0	≥30	n.r.	[79]
	ZrO₂.TODA	117	45	n.s.	90	90	5265	n.s.	10530	10530	1	≥50	n.r.	[11]
	ZrO₂.acrylate	117	70.5	141	70.5	141	8249	16497	8249	16497	0	≥50	n.r.	[11]
Nanosized organic pigments	DPP Orange N	64	n.s.	n.s.	45	n.s.	n.s.	n.s.	2880	n.s.	1	≥30	n.r.	[79]
Nanosized organic pigments	Pigment Blue 15:1	53	90	90	n.d.^c	n.s.	4770	4770	n.d.^c	n.s.	2	≥30	n.r.	[79]
Carbonaceous NM	Graphite nanoplatelets	74	n.s	45	90	n.s	n.s	3330	6660	n.s	1	≥10	n.r.	[82]

For all parameters, the significant in vitro LOAECs (significance as compared to the vehicle controls) are shown, both in mass/volume (µg/mL) and surface area/volume (mm²/mL) dose metrics (n.s.: no signficance). The surface area/volume-based values were calculated by multiplying the mass/volume values by the respective NM’s BET surface area. Surface area/volume-based values that undercut the in vitro threshold of 6000 mm²/mL are provided in italics. For test material assignment as either active (significant LOAEC < 6000 mm²/mL, ≥ 2 of 4 parameters affected) or passive (0 or only 1 parameter affected), the frequency of affected parameters is indicated in the column ‘threshold < 6000 mm²/mL’. Further, available rat STIS NOAEC values are provided for all test materials (and LOAEC values, if effects were observed). For both the in vitro and in vivo data, values indicating ‘activity’ are highlighted in bold italic
^an.r.: If no effects were observed in the STIS up to the highest tested concentration, no LOAEC was recorded (n.r.)
^bSince AlOOH was tested for 28 days (i.e., four consecutive 5-day exposure periods), the NOAEC that Pauluhn [58] recorded for this material (i.e., 3 mg/m³) was converted to a 5-day NOAEC by multiplying it by a factor of four [94]. Accordingly, the calculated 5-day NOAEC of 12 mg/m³ indicates passivity
^cFor technical reasons, TNF-α was not determined (n.d.) for Pigment Blue 15:1. However, since significant in vitro LOAECs below the threshold were recorded for LDH and GLU, this does not impair its assignment as ‘in vitro active’
^dNumbers in brackets apply to (short-term) inhalation studies as listed in the reference section

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